Epoxides stereoselective reductions

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

In addition to the above hydrolysis reactions, dinuclear approach to providing joint Lewis acid activation and nucleophile activation has been applied to other organic reactions (Figure 6.14) including stereoselective ring-opening of epoxides (18) [65, 66], stereoselective aldol condensation (19) [67, 68], and stereoselective reduction (20) reactions [69]. 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

Oxirane cleavage. Isobe and co-workers effected the stereoselective reduction of 1 to 2 by sequential treatment of the epoxide with sodium cyanoborohydride in anhydrous HMPT and diborane in THF. The authors suggest that this reaction involves internal hydride transfer in the hypothetical intermediate 3. Reduction in DME or THF results in products with the opposite configuration at C7. 

Reduction of ot-keto epoxides. Epoxidation of cyclic allylic alcohols results mainly in the epoxide syn to the hydroxyl group (4, 76). Schlessinger et al. have reported a method for isomerization of the alcohol group by oxidation to the ketone and reduction to the anh-alcohol. In a model case, 2->4, pyridinium chloro-chromate buffered with sodium acetate was found to be the most satisfactory oxidant. Stereoselective reduction to 4 was found to be a more difficult problem, but eventually triisobutylaluminum was found to effect this reduction in high yield. 

Zinc borohydride was effective for the reduction of a,P-epoxy ketones (49) to the corresponding anti-a,3-epoxy alcohols (50) in ether at 0 °C irrespective of the substituents on the epoxide (equation 14). The selectivity was rationalized by intramolecular hydride delivery from a five-membered zinc chelate avoiding the epoxide ring. In a limited study of the stereoselective reduction of y,8-epoxy ketones (51), LAH and di-2-(o-toluidinomethyl)pyrrolidine in ether at -78 C gave the desired c/j-epoxy alcohols (52) required for ionophore synthesis with good selectivity (>10 1) (equation 15). ... 

The importance of optically active vicinal thio- and selenoalcohols has been recognized as potential intermediates for enantiomerically pure epoxides, which have been used in the synthesis of more complex enantiomerically enriched compounds [54]. The synthesis of racemic vicinal thio- and selenoalcohols via stereoselective reduction of a-thio- [55] and a-selenoketones [56] has been reported, whereas very few asymmetric syntheses of highly optically active vicinal thioalcohols are known [57]. 

Conjugate reduction of a,fi-unsaturated epoxides.4 Reduction of 2-methyl-l,2-oxido-3-butene (l)5 with DIBAH in refluxing hexane results in highly stereoselective conjugate addition to give the Z alcohol (2) the E isomer (3) is a minor product. 

In addition to the above described procedures implying either direct oxidation of an olefinic double bond or stereoselective reduction of a ketone precursor, which, as discussed above, do not really provide very efficient ways for the large scale synthesis of enantiopure epoxides, some indirect strategies have also been explored. These are essentially based on the resolution of epoxide-ring bearing substrates as exemplified below. As will be seen, these approaches imply the use of cofactor-independent enzymes, which are in practice much easier to work with, and lead to very interesting results. As a matter fact, some of these processes are already used on an industrial scale, and it can be predicted that future industrial applications will continue to be essentially based on the use of these very promising easy-to-use biocatalysts. 

In Sequence 3, one of the necessary inversions was effected by a highly stereoselective reduction of ketone 62 with the hindered reagent lithium perhydro-9B-boraphenalylhydride to obtain alcohol 63. Conversion of the terminal epoxide 64a to the desired cw-(5/ )-55 was unexpectedly difficult, as compared with the corresponding reaction in Sequence 1. The difficulty was ascribed to steric... 

The stereoselective reduction of a-alkylthio ketones has been investigated in some detail because of the potential of the product /(-hydroxy sulfides as intermediates for the synthesis of epoxides and alkenes. 

Hie an /-diastereomers 19 and 23 are available via the inversion of the 3- or 4-OH-functions of 10 (Scheme 4). This is achieved via monoprotection of 10 to benzoate 15, oxidation to ketone 16, stereoselective reduction to 17 and formation of epoxide 18, which is C2-symmetrical and thus can only give the anti-HM derivative 19 on cuprate addition. Alternatively 17 is converted into 20 which gives the C2-symmetrical epoxide 22 via 21. Again only one HM-derivative, namely 23, can be formed on reaction with the dimethyl cuprate (3). 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

Bottrospicatol (92a ) was prepared by epoxidation of (-)-carvone (93 ) with mCPBA to (-)-carvone-8,9-epoxide (96 ), followed by stereoselective reduction with NaBH4 to alcohol, which was immediately cyclized with 0.1 N H2SO4 to give diastereomixture of bottrospicatol (92a and b ) (Nishimura et ah, 1983a) (Figure 19.84). 

Oxidation of cyclohexene by a peroxyacid (Section 11.8Q gives an epoxide. Stereoselective nucleophilic attack by azide ion anti to the leaving oxygen of the epoxide ring (Section 11.9B) followed by reduction of the azide with lithium aluminum hydride gives racemic fra s-2-aminocyclohexanol. 

The stereoselective reduction of cyclic a, 8-unsaturated epoxides by diborane has recently been extended to acyclic cases (Scheme 16) and shown" to produce (Z)-alkene geometry independent of the substitution pattern, suggesting an intramolecular conjugate reduction (36). 

---